足部アライメントと後足部運動学は変形性膝関節症患者に対する外側楔状足底挿板の膝関節内転モーメント軽減効果に影響を及ぼす

広島大学(Hiroshima University)博士(保健学)Doctor of Philosophy in Health Sciencedoctora

Open Multi-Access Network Platform with Dynamic Task Offloading and Intelligent Resource Monitoring

We constructed an open multi-access network platform using open-source hardware and software. The open multi-access network platform is characterized by the flexible utilization of network functions, integral management and control of wired and wireless access networks, zero-touch provisioning, intelligent resource monitoring, and dynamic task offloading. We also propose an application-driven dynamic task offloading that utilizes intelligent resource monitoring to ensure effective task processing in edge and cloud servers. For this purpose, we developed a mobile application and server applications for the open multi-access network platform. To investigate the feasibility and availability of our developed platform, we experimentally and analytically evaluated the effectiveness of application-driven dynamic task offloading and intelligent resource monitoring. The experimental results demonstrated that application-driven dynamic task offloading could reduce real-time task response time and traffic over metro and core networks

Cold-induced metabolic conversion of haptophyte di- to tri-unsaturated C37 alkenones used as palaeothermometer molecules

The cosmopolitan marine haptophyte alga Emiliania huxleyi accumulates very long-chain (C37-C40) alkyl ketones with two to four trans-type carbon-carbon double bonds (alkenones). These compounds are used as biomarkers of haptophytes and as palaeothermometers for estimating sea-surface temperatures in biogeochemistry. However, the biosynthetic pathway of alkenones in algal cells remains enigmatic, although it is well known that the C37 tri-unsaturated alkenone (K37:3) becomes dominant at low temperatures, either by desaturation of K37:2 or by a separate pathway involving the elongation of tri-unsaturated alkenone precursors. Here, we present experimental evidence regarding K37:3 synthesis. Using the well-known cosmopolitan alkenone producer E. huxleyi, we labelled K37:2 with 13C by incubating cells with 13C-bicarbonate in the light at 25 °C under conditions of little if any K37:3 production. After stabilisation of the 13C-K37:2 level by depleting 13C-bicarbonate from the medium, the temperature was suddenly reduced to 15 °C. The 13C-K37:2 level rapidly decreased, and the 13C-K37:3 level increased, whereas the total 13C-K37 level—namely [K37:2 + K37:3]—remained constant. These 13C-pulse-chase-like experimental results indicate that 13C-K37:2 is converted directly to 13C-K37:3 by a desaturation reaction that is promoted by a cold signal. This clear-cut experimental evidence is indicative of the existence of a cold-signal-triggered desaturation reaction in alkenone biosynthesis

Daily intake of Lactobacillus gasseri CP2305 relieves fatigue and stress-related symptoms in male university Ekiden runners : A double-blind, randomized, and placebo-controlled clinical trial

The heat-inactivated, enteric-colonizing Lactobacillus gasseri CP2305 (CP2305) ameliorates psychological stress-related symptoms. In this study, we examined effects of CP2305 on top athletes experiencing physical and mental stresses. Forty-nine male university Ekiden (long distance relay race) runners daily took the CP2305-containing beverage for 12 weeks during training for and competing in All-Japan university championships. The CP2305 intake significantly facilitated recovery from fatigue and relieved anxiety and depressive mood, compared with placebo intake. The CP2305 intake significantly prevented the training-induced reduction of hemoglobin and facilitated exercise-induced increase in serum growth hormone levels. The CP2305 intake significantly increased the alpha- and beta-diversities of fecal microbiota, and the compositions of Bifidobacterium and Faecalibacterium. Gene expression profiling of peripheral blood leukocytes indicated that CP2305 prevented the stress-induced changes in the expression of genes related to mitochondrial functions. Our results suggest that daily intake of paraprobiotic CP2305 may be beneficial to athletes facing stressful situations

Daily administration of paraprobiotic Lactobacillus gasseri CP2305 ameliorates chronic stress-associated symptoms in Japanese medical students

Administration of Lactobacillus gasseri CP2305 for 4 weeks improved stress-associated behaviours in healthy young adults and clinical symptoms in patients with irritable bowel syndrome. The present study was designed to confirm the stress-relieving effects of heat-inactivated, washed CP2305 (paraprobiotic CP2305) on 69 sixth-year medical students (40 males and 29 females) preparing to take the national examination for medical practitioners. Administration of the paraprobiotic CP2305 for 12 weeks significantly improved sleep quality assessed by both the Pittsburgh Sleep Quality Index and a one-channel sleep electroencephalogram during the pre-examination period compared with that of the placebo administration. The paraprobiotic CP2305 administration also prevented increases in basal salivary cortisol release and expression of stress-responsive microRNAs (miR-144 and miR-144⁄). In addition to the improvement in parasympathetic nerve activity, the paraprobiotic CP2305 normalized the bowel habits under the stressful conditions. Based on these results, we propose that paraprobiotic CP2305 may be used as a para-psychobiotic

Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae

ABSTRACT To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

慢性期移植腎機能低下例におけるIV型コラーゲンの分布の変化に関する検討

IV型コラーゲンは基底膜の主要構成成分であり,生体内に広く分布している.移植後急性期腎機能低下例においては,腎臓のIV型コラーゲン分布に変化が認められる.今回我々は移植腎機能廃絶の主原因である慢性期移植腎機能低下症(chronic allograft nephropathy: CAN)におけるIV型コラーゲンの変化について検討した.当院において施行された腎移植患者を,移植腎機能に基づいて以下の群に分類し,組織所見について検討した.なおCAN症例は,光学顕微鏡所見で診断された症例を用いた.Group A(n=5):腎機能正常群,Group B(n=10):急性期移植腎機能低下群,Group C(n=35): CAN症例で血清クレアチニン値2～4mg/dl,Group D(n=15): CANで血清クレアチニン値>4mg/dl.各症例におけるIV型コラーゲン分布について,IV型コラーゲンのα1鎖に対するモノクローナル抗体であるJK199,JK132を用いて,蛍光顕微鏡により検討した.Group AではJK199,JK132ともにメサンギウム基質(MM),ボーマン嚢基底膜(BBM),尿細管基底膜(TBM)に対する反応のみを認めた.Group Bでは,JK199はMM,BBM,TBMに加え,糸球体基底膜(GBM)および腎間質(INS)に対する反応を認めた.JK132の反応性はGroup Aと同様であった.一方,Group CおよびGroup Dでは,JK199においてはMM,GBM,BBM,TBM,INSに対する反応性が増強していた.JK132についてはMM,BBM,TBMに加え,GBMおよびINSにおいても反応が認められた.また,JK199およびJK132の反応性はGroup CよりもGroup Dにおいて強い傾向が認められた.GBMおよびINSにおけるJK132の反応陽性化はCANに特異的な所見であることが示唆された.Previously, we demonstrated the altered formation of collagen IV, which is the main constituent of the basement membrane, in renal allografts by staining with two monoclonal antibodies against the α1 chain of collagen IV. In the present study, we investigated the alteration of collagen IV in chronic allograft nephropathy (CAN), which is an irreversible change that can occur in renal allografts. Biopsy specimens of normal kidneys (Group A: n=5) and acute rejection (Group B: n=10) were studied as controls. Fifty biopsy specimens from 41 patients who had been diagnosed as having CAN were divided into two groups, according to renal function: Group C (n=35), sCr 2～4 mg/dl, and Group D (n=15), sCr>4 mg/dl. Two monoclonal antibodies, JK199 and JK132, those recognize the α1 chain of collagen IV were used. In Group A, JK199 reacted with the glomerular basement membrane (GBM), the mesangial matrix (MM), the basement membrane of Bowman's capsule (BBM) and the tubular basement membrane (TBM). JK132 only reacted with the MM, BBM and TBM. In Group B, JK199 reacted with GBM, MM, BBM, TBM and the interstitium (INS). JK132 only reacted with MM, BBM and TBM. In Group C and Group D, JK199 and JK132 reacted universally with GBM and INS in addition to MM, BBM and TBM. The intensity of the reaction was higher in Group D than in Group C. Thus, the reactivity of JK132 with GBM and INS was a unique finding for the CAN specimens. These results suggest that collagen IV is upregulated in CAN and the reactivity of JK132 in GBM and INS may represent the point of irreversible dysfunction of renal allografts